INVESTIGATION OF REISHI AS A NATURAL THERAPEUTIC FOR INFLAMMATORY BREAST CANCER

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 这项拟议的研究将调查含有灵芝全蘑菇化合物的膳食补充剂对炎性乳腺癌(IBC)发生和发展的体内抗癌作用。IBC是最致命也是最不为人所知的晚期乳腺癌。它的致命性源于它侵犯血管和淋巴系统的性质，以及没有典型的肿瘤肿块。灵芝化合物已被用于癌症，以改善免疫系统和杀死恶性肿瘤细胞。然而，热石提取物作为一种天然的靶向治疗IBC的作用尚未被研究。我们对人IBC细胞系的初步研究数据表明，整个蘑菇灵芝提取物通过影响与癌细胞存活、侵袭、转移和进展有关的基因来抑制IBC的进展。热石提取物选择性地抑制IBC细胞的生长和肿瘤环境的侵袭。此外，热石提取物抑制基质金属蛋白酶2和9的分泌，以及E-钙粘附素蛋白的表达，可能损害具有IBC表型特征的肿瘤球体形成能力，这是侵袭所必需的。我们的假设是灵石可以抑制IBC的发生和发展。我们的长期目标是确定整个蘑菇热石提取物的治疗效果，并研究热石影响IBC进展的分子机制。特异性AIM 1将利用新的成像技术确定整个蘑菇热石提取物对免疫低下小鼠IBC发生和发展的体内影响。特异性AIM2将在基因和蛋白质水平上描绘整个蘑菇灵芝提取物、淋巴结和原发肿瘤在安慰剂或灵芝提取物治疗后的分子靶点。具体目标3将详细说明为PI实现成功的独立研究生涯而进行的指导和职业发展计划。这项建议在评估膳食补充剂在局部浸润性乳腺癌中的作用方面是独一无二的。这项研究与公共卫生相关，因为它有望促进对整个蘑菇灵实膳食补充剂治疗这种致命疾病的治疗机制的理解和检测，并对IBC患者、高危患者和IBC幸存者产生影响。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The proposed study will investigate the in vivo anti-cancer effects of a dietary supplement containing whole mushroom compounds of Reishi on Inflammatory Breast Cancer (IBC) onset and progression. IBC is the most lethal and least understood form of advanced breast cancer. Its lethality originates from its nature of invading the vascular and lymphatic systems and absence of a typical tumor mass. Reishi compounds have been used in cancer to improve the immune system and kill malignant cancer cells. However, the effect of Reishi extract as a natural targeted therapeutic on IBC has not been investigated. Our preliminary data studying a human IBC cell line shows that whole mushroom Reishi extract inhibits IBC progression by affecting genes that contribute to cancer cell survival, invasion, metastasis, and progression. Reishi extract selectively inhibits IBC cell growth and invasion of the tumor environment. Furthermore, Reishi extract inhibits matrix metalloproteinase 2 and 9 secretion, and E-cadherin protein expression, possibly impairing the capacity of tumor spheroid formation that is characteristic of the IBC phenotype, and a requirement for invasion. Our HYPOTHESIS is that Reishi inhibits IBC onset and progression. Our long-term OBJECTIVES are to determine the therapeutic efficacy of whole mushroom Reishi extract, and investigate the molecular mechanisms by which Reishi affects IBC progression. SPECIFIC AIM 1 will determine the in vivo effects of whole mushroom Reishi extract on IBC onset and progression in an immunocompromised mouse model using novel imaging techniques. SPECIFIC AIM 2 will delineate the molecular targets of whole mushroom Reishi extract lymph nodes and primary tumors at the gene and protein level following treatment with placebo or Reishi extract. SPECIFIC AIM 3 will detail the mentoring and career developmental plans for the PI to achieve a successful independent research career. This proposal is UNIQUE in evaluating a role for a dietary supplement in a locally invasive breast cancer. This research is RELEVANT to public health because it promises to advance the understanding and detection of the therapeutic mechanisms of whole mushroom Reishi dietary supplement for this fatal disease and impact IBC patients, those at risk, and survivors of IBC.